Graphene oxide quantum dots-loaded sinomenine hydrochloride nanocomplexes for effective treatment of rheumatoid arthritis via inducing macrophage repolarization and arresting abnormal proliferation of fibroblast-like synoviocytes.

The characteristic features of the rheumatoid arthritis (RA) microenvironment are synovial inflammation and hyperplasia. Therefore, there is a growing interest in developing a suitable therapeutic strategy for RA that targets the synovial macrophages and fibroblast-like synoviocytes (FLSs). In this study, we used graphene oxide quantum dots (GOQDs) for loading anti-arthritic sinomenine hydrochloride (SIN). By combining with hyaluronic acid (HA)-inserted hybrid membrane (RFM), we successfully constructed a new nanodrug system named HA@RFM@GP@SIN NPs for target therapy of inflammatory articular lesions. Mechanistic studies showed that this nanomedicine system was effective against RA by facilitating the transition of M1 to M2 macrophages and inhibiting the abnormal proliferation of FLSs in vitro. In vivo therapeutic potential investigation demonstrated its effects on macrophage polarization and synovial hyperplasia, ultimately preventing cartilage destruction and bone erosion in the preclinical models of adjuvant-induced arthritis and collagen-induced arthritis in rats. Metabolomics indicated that the anti-arthritic effects of HA@RFM@GP@SIN NPs were mainly associated with the regulation of steroid hormone biosynthesis, ovarian steroidogenesis, tryptophan metabolism, and tyrosine metabolism. More notably, transcriptomic analyses revealed that HA@RFM@GP@SIN NPs suppressed the cell cycle pathway while inducing the cell apoptosis pathway. Furthermore, protein validation revealed that HA@RFM@GP@SIN NPs disrupted the excessive growth of RAFLS by interfering with the PI3K/Akt/SGK/FoxO signaling cascade, resulting in a decline in cyclin B1 expression and the arrest of the G2 phase. Additionally, considering the favorable biocompatibility and biosafety, these multifunctional nanoparticles offer a promising therapeutic approach for patients with RA.

Development of graphitic carbon nitride quantum dots-based oxygen self-sufficient platforms for enhanced corneal crosslinking.

Keratoconus, a disorder characterized by corneal thinning and weakening, results in vision loss. Corneal crosslinking (CXL) can halt the progression of keratoconus. The development of accelerated corneal crosslinking (A-CXL) protocols to shorten the treatment time has been hampered by the rapid depletion of stromal oxygen when higher UVA intensities are used, resulting in a reduced cross-linking effect. It is therefore imperative to develop better methods to increase the oxygen concentration within the corneal stroma during the A-CXL process. Photocatalytic oxygen-generating nanomaterials are promising candidates to solve the hypoxia problem during A-CXL. Biocompatible graphitic carbon nitride (g-C3N4) quantum dots (QDs)-based oxygen self-sufficient platforms including g-C3N4 QDs and riboflavin/g-C3N4 QDs composites (RF@g-C3N4 QDs) have been developed in this study. Both display excellent photocatalytic oxygen generation ability, high reactive oxygen species (ROS) yield, and excellent biosafety. More importantly, the A-CXL effect of the g-C3N4 QDs or RF@g-C3N4 QDs composite on male New Zealand white rabbits is better than that of the riboflavin 5'-phosphate sodium (RF) A-CXL protocol under the same conditions, indicating excellent strengthening of the cornea after A-CXL treatments. These lead us to suggest the potential application of g-C3N4 QDs in A-CXL for corneal ectasias and other corneal diseases.

Biomolecule-regulation of fluorescent probe signaling: Homogeneous rapid portable protease sensing in serum.

BACKGROUND: As is well documented, prostate cancer (PCa) being the second most prevalent cancer in men worldwide, emphasizing the importance of early diagnosis for prognosis. However, conventional prostate-specific antigen (PSA) testing lacks sufficient diagnostic efficiency due to its relatively low sensitivity and limited detection range. Mounting evidence suggests that matrix metalloproteinase 9 (MMP-9) expression increases with the aggressive behavior of PCa, highlighting the significance of detecting the serum level of MMP-9 in patients. Developing a non-immune rapid, portable MMP-9 detection strategy and investigating its representativeness of PCa serum markers hold considerable implications. RESULTS: Herein, our study developed a simple, homogeneous dual fluorescence and smartphone-assisted red-green-blue (RGB) visualization peptide sensor of MMP-9, utilizing cadmium telluride quantum dots (CdTe QDs) and calcein as signal reporters. The essence of our approach revolves around the proteolytic ability of MMP-9, exploiting the selective recognition of molecule-Cu2+ complexes with different molecular weights by CdTe QDs and calcein. Under optimized conditions, the limits of detection (LODs) for MMP-9 were 0.5 pg/mL and 6 pg/mL using fluorescence and RGB values readouts, respectively. Indeed, this strategy exhibited robust specificity and anti-interference ability. MMP-9 was quantified in 42 clinical serum samples via dual-fluorescence analysis, with 12 samples being visually identified with a smartphone. According to receiver operating characteristic curve (ROC) analysis, its sensitivity and specificity were 90 % and 100 %, respectively, with an area under curve (AUC) value of 0.903. SIGNIFICANCE AND NOVELTY: Of note, the results of the aforementioned analysis were highly consistent with the serum level of PSA, clinical color Doppler flow imaging (CDFI), and histopathological results. Therefore, this simple, rapid, homogeneous fluorescence and visualization strategy can reliably measure MMP-9 levels and exhibit promising potential in point-of-care testing (POCT) applications for PCa patients.

Dual Functional Magnetic Nanoparticles Conjugated with Carbon Quantum Dots for Hyperthermia and Photodynamic Therapy for Cancer.

The global incidence of cancer continues to rise, posing a significant public health concern. Although numerous cancer therapies exist, each has limitations and complications. The present study explores alternative cancer treatment approaches, combining hyperthermia and photodynamic therapy (PDT). Magnetic nanoparticles (MNPs) and amine-functionalized carbon quantum dots (A-CQDs) were synthesized separately and then covalently conjugated to form a single nanosystem for combinational therapy (M-CQDs). The successful conjugation was confirmed using zeta potential, Fourier transform infrared spectroscopy (FT-IR), and UV-visible spectroscopy. Morphological examination in transmission electron microscopy (TEM) further verified the conjugation of CQDs with MNPs. Energy dispersive X-ray spectroscopy (EDX) revealed that M-CQDs contain approximately 12 weight percentages of carbon. Hyperthermia studies showed that both MNP and M-CQDs maintain a constant therapeutic temperature at lower frequencies (260.84 kHz) with high specific absorption rates (SAR) of 118.11 and 95.04 W/g, respectively. In vitro studies demonstrated that MNPs, A-CQDs, and M-CQDs are non-toxic, and combinational therapy (PDT + hyperthermia) resulted in significantly lower cell viability (~4%) compared to individual therapies. Similar results were obtained with Hoechst and propidium iodide (PI) staining assays. Hence, the combination therapy of PDT and hyperthermia shows promise as a potential alternative to conventional therapies, and it could be further explored in combination with existing conventional treatments.

Polaron engineering promotes NIR-II absorption of carbon quantum dots for bioimaging and cancer therapy.

Recent years have witnessed a surge of interest in tuning the optical properties of organic semiconductors for diverse applications. However, achieving control over the optical bandgap in the second near-infrared (NIR-II) window has remained a major challenge. To address this, here we report a polaron engineering strategy that introduces diverse defects into carbon quantum dots (CQDs). These defects induce lattice distortions resulting in the formation of polarons, which can absorb the near-field scattered light. Furthermore, the formed polarons in N-related vacancies can generate thermal energy through the coupling of lattice vibrations, while the portion associated with O-related defects can return to the ground state in the form of NIR-II fluorescence. On the basis of this optical absorption model, these CQDs have been successfully applied to NIR-II fluorescence imaging and photothermal therapy. This discovery could open a promising route for the polarons of organic semiconductor materials as NIR-II absorbers in nanomedical applications.

DNAzyme and controllable cholesterol stacking DNA machine integrates dual-target recognition CTCs enable homogeneous liquid biopsy of breast cancer.

Although circulating tumor cells (CTCs) have demonstrated considerable importance in liquid biopsy, their detection is limited by low concentrations and complex sample components. Herein, we developed a homogeneous, simple, and high-sensitivity strategy targeting breast cancer cells. This method was based on a non-immunological stepwise centrifugation preprocessing approach to isolate CTCs from whole blood. Precise quantification is achieved through the specific binding of aptamers to the overexpressed mucin 1 (MUC1) and human epidermal growth factor receptor 2 (HER2) proteins of breast cancer cells. Subsequently, DNAzyme cleavage and parallel catalytic hairpin assembly (CHA) reactions on the cholesterol-stacking DNA machine were initiated, which opened the hairpin structures T-Hg2+-T and C-Ag+-C, enabling multiple amplifications. This leads to the fluorescence signal reduction from Hg2+-specific carbon dots (CDs) and CdTe quantum dots (QDs) by released ions. This strategy demonstrated a detection performance with a limit of detection (LOD) of 3 cells/mL and a linear range of 5-100 cells/mL. 42 clinical samples have been validated, confirming their consistency with clinical imaging, pathology findings and the folate receptor (FR)-PCR kit results, exhibiting desirable specificity of 100% and sensitivity of 80.6%. These results highlight the promising applicability of our method for diagnosing and monitoring breast cancer.

Upconversion Nanoparticle-Based Dot-Blot Immunoassay for Quantitative Biomarker Detection.

Dot-blot immunoassays are widely used for the user-friendly detection of clinical biomarkers. However, the majority of dot-blot assays have only limited sensitivity and are only used for qualitative or semiquantitative analysis. To overcome this limitation, we have employed labels based on photon-upconversion nanoparticles (UCNPs) that exhibit anti-Stokes luminescence and can be detected without optical background interference. First, the dot-blot immunoassay on a nitrocellulose membrane was optimized for the quantitative analysis of human serum albumin (HSA), resulting in a limit of detection (LOD) of 0.19 ng/mL and a signal-to-background ratio (S/B) of 722. Commercial quantum dots were used as a reference label, reaching the LOD of 4.32 ng/mL and the S/B of 3, clearly indicating the advantages of UCNPs. In addition, the potential of UCNP-based dot-blot for real sample analysis was confirmed by analyzing spiked urine samples, reaching the LOD of 0.24 ng/mL and recovery rates from 79 to 123%. Furthermore, we demonstrated the versatility and robustness of the assay by adapting it to the detection of two other clinically relevant biomarkers, prostate-specific antigen (PSA) and cardiac troponin (cTn), reaching the LODs in spiked serum of 9.4 pg/mL and 0.62 ng/mL for PSA and cTn, respectively. Finally, clinical samples of patients examined for prostate cancer were analyzed, achieving a strong correlation with the reference electrochemiluminescence immunoassay (recovery rates from 89 to 117%). The achieved results demonstrate that UCNPs are highly sensitive labels that enable the development of dot-blot immunoassays for quantitative analysis of low-abundance biomarkers.

An electrochemical immunosensor based on MXene-GQD/AuNPs for the detection of trace amounts of CA-125 as specific tracer of ovarian cancer.

An electrochemical immunoassay system was developed to detect CA-125 using a glassy carbon electrode (GCE) modified with MXene, graphene quantum dots (GQDs), and gold nanoparticles (AuNPs). The combined MXene-GQD/AuNPs modification displayed advantageous electrochemical properties due to the synergistic effects of MXene, GQDs, and AuNPs. The MXene-GQD composite in the modified layer provided strong mechanical properties and a large specific surface area. Furthermore, the presence of AuNPs significantly improved conductivity and facilitated the binding of anti-CA-125 on the modified GCE, thereby enhancing sensitivity. Various analytical techniques such as FE-SEM and EDS were utilized to investigate the structural and morphological characteristics as well as the elemental composition. The performance of the developed immunosensor was assessed using electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV), square wave voltammetry (SWV), and differential pulse voltammetry (DPV). Under optimized conditions in a working potential range of -0.2 to 0.6 V (vs. Ag/AgCl), the sensitivity, linear range (LR), limit of detection (LOD), and correlation coefficient (R2) were determined to be 315.250 µA pU.mL-1/cm2, 0.1 to 1 nU/mL, 0.075 nU/mL, and 0.9855, respectively. The detection of CA-125 in real samples was investigated using the developed immunoassay platform, demonstrating satisfactory results including excellent selectivity and reproducibility.

Fluorescent carbon dots for discriminating cell types: a review.

Carbon dots (CDs) are quasi-spherical carbon nanoparticles with excellent photoluminescence, good biocompatibility, favorable photostability, and easily modifiable surfaces. CDs, serving as fluorescent probes, have emerged as an ideal tool for cellular differentiation owing to their outstanding luminescence performance and tunable surface properties. In this review, we summarize the recent research progress with CDs in the differentiation of cancer/normal cells, Gram-positive/Gram-negative bacteria, and live/dead cells, as well as the cellular differences used for differentiation. Additionally, we summarize the preparation methods, raw materials, and properties of the CDs used for cell discrimination. The differentiation mechanisms and the advantages or limitations of the differentiation methods are also introduced. Finally, we propose several research challenges in this field and future research directions that require extensive investigation. It is hoped that this review will help researchers in the design of new CDs as ideal fluorescent probes for realizing diverse cell differentiation applications.

Ultrabright NIR-IIb Fluorescence Quantum Dots for Targeted Imaging-Guided Surgery.

Pioneering approaches for precise tumor removal involve fluorescence-guided surgery, while challenges persist, including the low fluorescence contrast observed at tumor boundaries and the potential for excessive damage to normal tissue at the edges. Lead/cadmium sulfide quantum dots (PbS@CdS QDs), boasting high quantum yields (QYs) and vivid fluorescence, have facilitated advancements in the second near-infrared window (NIR-II, 900-1700 nm). However, during fluorescent surgical navigation operations, hydrophilic coatings of these inorganic nanoparticles (NPs) guarantee biosafety; it also comes at the expense of losing a significant portion of QY and NIR-II fluorescence, causing heightened damage to normal tissues caused by cutting edges. Herein, we present hydrophilic core-shell PbS@CdS@PEG NPs with an exceptionally small diameter (∼8 nm) and a brilliant NIR-IIb (1500-1700 nm) emission at approximately 1600 nm. The mPEG-SH (MW: 2000) addresses the hydrophobicity and enhances the biosafety of PbS@CdS QDs. In vivo fluorescence-guided cervical tumor resection becomes achievable immediately upon injection of an aqueous solution of PbS@CdS@PEG NPs. Notably, this approach results in a significantly reduced thickness (100-500 µm) of damage to normal tissues at the margins of the resected tumors. With a high QY (∼30.2%) and robust resistance to photobleaching, NIR-IIb imaging is sustained throughout the imaging process.

Designable Nanoadaptor for Enhanced Recognition of Natural Killer Cell to Tumor via Bio-orthogonal Click Reaction.

Highly efficient recognition of cancer cells by immune cells is important for successful therapeutic-cell-based cancer immunotherapy. Herein, we present a facile NIR-II nanoadaptor [hyaluronic acid (HA)/dibenzocyclooctyne (DBCO)-Au:Ag2Te quantum dots (QDs)] for enhancing the tumor recognition and binding ability of natural killer (NK) cells via a bio-orthogonal click reaction in vivo. The Nanoadaptor possesses superior tumor-targeting capacity, facilitating the accumulation of the chemical receptor DBCO at the tumor sites. Subsequently, the enrichment of DBCO on tumor cell surfaces provides multivalent recognition sites for capturing pretreated azide engineered NK92 cells (NK92-N3) through an efficient click reaction, thereby significantly enhancing the therapeutical efficiency. The dynamic process of nanoadaptor-mediated recognition of NK cells to tumor cells could be vividly observed using multiplexed NIR-II fluorescence imaging in a mouse model of lung cancer. Such a nanoadaptor strategy can be extended to other therapeutic cellular systems and holds promise for future clinical applications.

Si, O-Codoped Carbonized Polymer Dots with High Chemiresistive Gas Sensing Performance at Room Temperature.

A new type of carbonized polymer dot was prepared by the one-step hydrothermal method of triethoxylsilane (TEOS) and citric acid (CA). The sensor made from carbonized polymer dots (CPDs) showed superior gas sensing performance toward ammonia at room temperature. The Si, O-codoped CPDs exhibited superior ammonia sensing performance at room temperature, including a low practical limit of detection (pLOD) of 1 ppm (Ra/Rg: 1.10, 1 ppm), short response/recovery time (30/36 s, 1 ppm), high humidity resistance (less than 5% undulation when changing relative humidity to 80 from 30%), high stability (less than 5% initial response undulation after 120 days), reliable repeatability, and high selectivity against other interferential gases. The gas sensing mechanism was investigated through control experiments and in situ FTIR, indicating that Si, O-codoping essentially improves the electron transfer capability of CPDs and synergistically dominates the superior ammonia sensing properties of the CPDs. This work presents a facile strategy for constructing novel high-performance, single-component carbonized polymer dots for gas sensing.

Novel Lipid Nanocomplex Co-Carrying Bcl2 siRNA and Quantum Dots for EGF Receptor-Targeted Anti-Cancer Theranosis.

Many different types of nanoparticles have been suggested for tumor-targeted theranosis. However, most systems were prepared through a series of complicated processes and could not even overcome the blood-immune barriers. For the accurate diagnosis and effective treatment of cancers, herein we suggested the lipid micellar structure capturing quantum dot (QD) for cancer theranosis. The QD/lipid micelles (QDMs) were prepared using a simple self-assembly procedure and then conjugated with anti-epidermal growth factor receptor (EGFR) antibodies for tumor targeting. As a therapeutic agent, Bcl2 siRNA-cholesterol conjugates were loaded on the surface of QDMs. The EGFR-directed QDMs containing Bcl2 siRNA, so-called immuno-QDM/siBcl2 (iQDM/siBcl2), exhibited the more effective delivery of QDs and siBcl2 to target human colorectal cancer cells in cultures as well as in mouse xenografts. The effective in vivo targeting of iQDM/siBcl2 resulted in a more enhanced therapeutic efficacy of siBcl2 to the target cancer in mice. Based on the results, anti-EGFR QDM capturing therapeutic siRNA could be suggested as an alternative modality for tumor-targeted theranosis.

Ultrasmall Carbon Nanodots as Theranostic Nanoheaters for Precision Breast Cancer Phototherapy: Establishing the Translational Potential in Tumor-in-a-Dish Models.

This study investigates the remarkable attributes of sulfur-doped carbon nanodots (CDs) synthesized in high yield and a narrow size distribution (4.8 nm). These CDs exhibit notable features, including potential bioelimination through renal clearance and efficient photothermal conversion in the near-infrared region with multicolor photoluminescence across the visible spectrum. Our research demonstrates high biocompatibility and effective near-infrared (NIR)-triggered photothermal toxicity when targeting mammospheres and patient-derived tumor organoids. Moreover, the study delves into the intricate cellular responses induced by CD-mediated hyperthermia. This involves efficient tumor mass death, activation of the p38-mitogen-activated protein kinase (MAPK) pathway, and upregulation of genes associated with apoptosis, hypoxia, and autophagy. The interaction of CDs with mammospheres reveals their ability to penetrate the complex microenvironment, impeded at 4 °C, indicating an energy-dependent endocytosis mechanism. This observation underscores the CDs' potential for targeted drug delivery, particularly in anticancer therapeutics. This investigation contributes to understanding the multifunctional properties of sulfur-doped CDs and highlights their promising applications in cancer therapeutics. Utilizing 3-D tumor-in-a-dish patients' organoids enhances translational potential, providing a clinically relevant platform for assessing therapeutic efficacy in a context mirroring the physiological conditions of cancerous tissues.

A cellulose nanocrystal-based dual response of photonic colors and fluorescence for sensitive benzene gas detection.

Benzene, as a common volatile organic compound, represents serious risk to human health and environment even at low level concentration. There is an urgent concern on visualized, sensitive and real time detection of benzene gases. Herein, by doping Fe3+ and graphene quantum dots (GQDs), a cellulose nanocrystal (CNC) chiral nematic film was designed with dual response of photonic colors and fluorescence to benzene gas. The chiral nematic CNC/Fe/GQDs film could respond to benzene gas changes by reversible motion. Moreover, chiral nematic film also displays reversible responsive to humidity changes. The resulting CNC/Fe/GQDs chiral nematic film showed excellent response performance at benzene gas concentrations of 0-250 mg/m3. The maximal reflection wavelength film red shifted from 576 to 625 nm. Furthermore, structural color of CNC/Fe/GQDs chiral nematic film change at 44 %, 54 %, 76 %, 87 %, and 99 % relative humidity. Interestingly, due to the stability of GQDs to water molecules, CNC/Fe/GQDs chiral nematic film exhibit fluorescence response to benzene gas even in high humidity (RH = 99 %) environment. Besides, we further developed a smartphone-based response network system for quantitively determinization and signal transformation. This work provides a promising routine to realize a new benzene gas response regime and promotes the development of real-time benzene gas detection.

The influence of near-infrared carbon dots on the conformational variation and enzymatic activity of glucose oxidase: A multi-spectroscopic and biochemical study with molecular docking.

In recent years, the exceptional biocatalytic properties of glucose oxidase (GOx) have spurred the development of various GOx-functionalized nanocatalysts for cancer diagnosis and treatment. Carbon dots, renowned for their excellent biocompatibility and distinctive fluorescence properties, effectively incorporate GOx. Given the paramount importance of GOx's enzymatic activity in therapeutic efficacy, this study conducts a thorough exploration of the molecular-level binding dynamics between GOx and near-infrared carbon dots (NIR-CDs). Utilizing various spectrometric and molecular simulation techniques, we reveal that NIR-CDs form a ground-state complex with GOx primarily via hydrogen bonds and van der Waals forces, interacting directly with amino acid residues in GOx's active site. This binding leads to conformational change and reduces thermal stability of GOx, slightly inhibiting its enzymatic activity and demonstrating a competitive inhibition effect. In vitro experiments demonstrate that NIR-CDs attenuate the GOx's capacity to produce H2O2 in HeLa cells, mitigating enzyme-induced cytotoxicity and cellular damage. This comprehensive elucidation of the intricate binding mechanisms between NIR-CDs and GOx provides critical insights for the design of NIR-CD-based nanotherapeutic platforms to augment cancer therapy. Such advancements lay the groundwork for innovative and efficacious cancer treatment strategies.

Radish residue carbon dots-based novel starch/chitosan film with high antioxidant, biocompatibility, and antibacterial activities for salmon fillets' active packaging.

The corruption of refrigerated marine fish results in global economic losses exceeding 25 billion euros annually. However, conventional preservatives present challenges, including singular functionality, potential toxicity, and high cost. In response, we developed multifunctional, safe, cost-effective, and environmentally friendly carbon dots derived from radish residues (R-CDs) by using the one-pot hydrothermal method. The surface of R-CDs is enriched with hydroxyl groups, conferring broad-spectrum antioxidant and antibacterial characteristics. R-CDs exhibited a notable 72.92 % inhibition rate on lipid peroxidation, surpassing the effectiveness of vitamin C (46 %). Additionally, R-CDs demonstrated impressive scavenging rates of 93.8 % for 2,2-diphenyl-1-picrylhydrazyl free radicals and 99.36 % for 2,2-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid-free radicals. In combating spoilage bacteria such as Aeromonas sobria and Hafnia alvei, R-CDs disrupted cell structures and influenced intracellular substance content. Importantly, co-cultivation with R-CDs showed no significant cytotoxicity. Further incorporating R-CDs into films using starch and chitosan (S/CS/R-CDs films) for efficient and convenient use in salmon fillets preservation. S/CS/R-CDs films effectively inhibited the growth of spoilage bacteria, lipid oxidation, and protein decomposition in salmon fillets, thereby extending shelf life by 4 days. This combination of antioxidant and antibacterial properties in R-CDs, along with the functional films, presents a promising approach for enhancing salmon fillet preservation.

The ECL enhancement of MBene QDs with nanoparticle-on-mirror structure for sensitive detection of exosomal miRNA.

Thyroid cancer is the most prevalent endocrine malignancy. The development of sensitive and reliable methods to detect the thyroid cancer is the currently urgent requirement. Herein, we developed an electrochemiluminescence (ECL) biosensor based on MBene derivative quantum dots (MoB QDs) and Ag NP-on-mirror (NPoM) nanocavity structure. On the one hand, MBene QDs as a novel luminescent material in the ECL process was reported for the first time, which can react with H2O2 as co-reactant. On the other hand, the NPoM nanostructure was successfully constructed with the Ag mirror and Ag NPs to provide highly localized hot spots. The NPoM structure had high degree of light field confinement and electromagnetic field enhancement, which can amplify the ECL signal as the signal modulator. Therefore, the synergistic effect of the nanocavity and localized surface plasmon resonance (LSPR) mode in the NPoM facilitated the enhancement of the ECL signal of MoB QDs over 21.7 times. Subsequently, the proposed ECL biosensing system was employed to analyze the expression level of miRNA-222-3p in the thyroid cancer exosome. The results indicated the relative association between miRNA-222-3p and BRAFV600E mutation. The MoB QDs/NPoM biosensor displayed the ideal potential in assessing thyroid cancer progression for advancing clinical diagnosis applications.

NIR-emissive carbon nanodots as a tool to mark ribosomal RNA and nucleolus components using super-resolution microscopy.

Ribosomal RNA (rRNA) plays a key role in protein synthesis and ribosomal biogenesis. The exclusively used commercial dye for RNA staining is SYTO RNASelect, which works in fixed cells only. To overcome this constraint, we synthesized NIR-emissive, highly photostable, and biocompatible carbon nanodots (CNDs) as a fluorescent biomarker for rRNA. The synthesized CNDs could stain rRNA in both live and fixed cells. We were able to visualize rRNA at different sites in eukaryotic cells using super-resolution microscopy (SRM). The CNDs localized rRNA in the dense fibrillar components (DFCs) of the nucleolus, nuclear membrane, and rough endoplasmic reticulum (RER). The super-resolved hollow ring-structured DFC with an FWHM of 140 nm, nuclear membrane with an FWHM of 120 nm, and ER with an FWHM of 115 nm were observed. We further found a marked contrast between the pre-RNA synthesized in cancer cells and normal cells. We believe that these CNDs have great potential in rRNA imaging and comprehending the complex relationships between rRNA dynamics and basic biological processes, disease development, or drug interactions.

CRISPR/Cas12a trans-cleavage mediated photoelectrochemical biosensor based on zeolitic imidazolate framework-67 for ATP determination.

An efficient PEC biosensor is proposed for ATP detection based on exciton energy transfer from CdTe quantum dots (CdTe QDs) to Au nanoparticles (AuNPs), integrating CRISPR/Cas12a trans-cleavage activity and specific recognition of ZIF-67 to ATP. Exciton energy transfer between CdTe QDs and AuNPs system is firstly constructed as photoelectrochemical (PEC) sensing substrate. Then, the activator DNAs, used to activate CRISPR/Cas12a, are absorbed on the surface of ZIF-67. In the presence of ATP, the activator DNAs are released due to more efficient adsorption of ZIF-67 to ATP. The released activator DNA activates trans-cleavage activity of CRISPR/Cas12a to degrade ssDNA on the electrode, leading to the recovery of photocurrent due to the interrupted energy transfer. Benefiting from the specific recognition of ZIF-67 to ATP and CRISPR/Cas12a-modulated amplification strategy, the sensor is endowed with excellent specificity and high sensitivity.